Elizabeth J. Samelson, PhD, is a well-trained musculoskeletal epidemiologist planning to develop new skills and expertise to investigate potential shared mechanisms underlying the relation between osteoporosis and vascular calcification. Specifically, the immediate career goal of the proposed training and research program is for the candidate to develop new skills and knowledge in two areas: (1) the biology of bone and vascular calcification and (2) the use of quantitative compute tomography (QCT) bone densitometry techniques to investigate the relation between bone and vascular calcification. The long-term career goal is for the candidate to become an independent investigator in the area of musculoskeletal disease and an expert in bone and vascular calcification, a new and poorly understood area, with the ultimate public health goal to help reduce the risk of osteoporosis (and possibly, in conjunction, atherosclerosis) and its devastating impact on elderly women and men. The research career development plan involves frequent, formal interactions with mentors who are independently funded, senior investigators with comprehensive and complementary areas of expertise and programs in osteoporosis epidemiology, vascular calcification, and bone imaging. Training will include participation in intensive, comprehensive courses and interdisciplinary research seminars conducted in the outstanding research environment in Boston, including the Institute for Aging Research (IFAR) at Hebrew SeniorLife (HSL), Harvard Medical School (HMS) and its affiliated institutions (Beth Israel Deaconess Medical Center, Massachusetts General Hospital), as well as the Framingham Study. The purpose of this study is to use QCT images performed in 3500 participants of the Framingham QCT Study (a large, community-based study of 1800 men and 1700 women, ages 40 through 90 years, mean 61 years) to determine volumetric, trabecular bone mineral density (vTBMD) of the spine and assess the relation between vTBMD level and severity of vascular calcification (assessed on the same scans). The study will use reliable, validated techniques to analyze the QCT images and combine these data with clinical information rigorously acquired for Framingham participants. Finally, the study will test the hypothesis that vTBMD will be positively related to serum level of osteoprotegerin (OPG), and inversely related to receptor activator of nuclear factor K-beta ligand (RANKL), and that OPG will explain a statistically significant proportion of the inverse correlation between vTBMD and vascular calcification in women and men. The relevance of the proposed study is that the results will improve understanding of the possible causes of osteoporosis also involved with the development of cardiovascular disease. Thus, the results of this study could lead to future therapies to treat and or event both osteoporosis and cardiovascular disease.